Age-related loss of muscle function and mass occurs inevitably in all individuals, however its progression depends on a range of genetic and environmental factors, such as physical activity and nutritional intake.
In some subjects, the effect of ageing on muscle may progress to a state of morbidity, specific conditions of which include sarcopenia and frailty. Sarcopenia is defined as occurring at the point at which the age-related loss of muscle function and mass becomes debilitating and impacts on quality of life (Sayer, A. A. et al. (2013) Age Ageing 42: 145-150). In contrast, frailty is a classification of age-related muscle dysfunction which relies on muscle strength and functionality, but not muscle mass (Morley, J. E. et al. (2013) J. Am. Med. Dir. Assoc. 14: 392-397).
Sarcopenia and frailty are multi-factorial syndromes which associate with pathophysiological changes, such as impaired neuro-muscular transition, altered excitation/contraction coupling, impaired regenerative capacity linked to stem cell exhaustion, defects of mitochondrial and energy metabolism in myofibers, and marbling of skeletal muscle with fat and fibrosis (Ali, S. et al. (2014) Gerontology 60: 294-305). The aetiology of these syndromes is therefore complex and poorly understood, but low physical activity, hormonal decline in anabolic hormones (e.g. androgens and IGF-1), and malnutrition and/or nutritional deficiencies play an important role (Mithal, A. et al. (2013) Osteoporos. Int. 24: 1555-1566).
Sarcopenia is becoming a major health concern in developed countries, where lessened physical activity with age and increased longevity are particularly prevalent. In severe cases, sarcopenia may result in a person losing their ability to live independently. In addition, sarcopenia is a predictor of wider-ranging disability in population-based studies, and has been linked to poor balance, gait speed, prevalence of falls and fractures.
Reduced physical activity is thought to increase the likelihood of sarcopenia and therefore increased exercise will likely be beneficial in combating the condition. Indeed, resistance exercise is associated with increased synthesis of proteins in skeletal muscle. However, exercise as a treatment often suffers from poor patient compliance.
There are currently no pharmacological agents approved for the treatment of sarcopenia. A number of growth hormones have been studied in this context, however these have shown little effect. In addition, anabolic steroids may increase muscle mass and strength, but are associated with a number of side effects, such as increased risk of prostate cancer. Moreover, existing pharmacological and nutritional approaches are mainly directed at targeting muscle anabolism and do not adequately address the neuromuscular defects associated with the condition.
Accordingly there remains a significant need for methods of maintaining or increasing muscle function and mass in ageing subjects. In particular, there is a need for methods of treating sarcopenia and frailty.